The studies described in this proposal are part of a systematic program directed toward the development of biochemical methods by which the status and function of the sympathetic nervous system may be measured in man. The development of these methods necessarily involves an enlargment of our understanding of the biochemistry and function of the adrenergic nerve terminal. The experiments proposed here focus on the measurement of the catecholamine biosynthetic enzyme dopamine-beta-hydroxylase (DBH) and the degradative enzyme catechol-0-methyltransferase (COMT) in blood, an easily sampled human tissue. The proposed studies will investigate the relationship of these two enzyme activities in blood to their activities in neuronal and other tissues. Special emphasis will be placed on the importance of genetic and developmental factors that may strongly influence values of serum DBH and erythrocyte COMT activity in individual subjects. Studies of DBH will include experiments in which clones of neuroblastoma cells, a system that has been used as a model of the adrenergic neuron, will be utilized to investigate the mechanism of DBH and neurotransmitter release. Studies of changes in serum DBH with growth and development and of the metabolic fate of the circulating enzyme in experimental animals will also be carried out. Experiments on erythrocyte COMT activity will include investigation of the mode of inheritance of the enzyme activity in man, of the biochemical basis of differences in COMT activity in human blood and of changes in COMT activity in experimental animals with growth and development. These experiments represent one step toward the development of the ability to characterize by biochemical techniques the function and status of the adrenergic neuron in the intact organism. In addition, the results of these studies will enlarge our understanding of the function of this portion of the nervous system.